This application is for the establishment of a center at the University of Delaware for research in structural and functional genomics. The center will hold the infrastructure and expertise base to address biomedical questions by identifying key proteins in genomic databases using functional genomics techniques, determining their structures and how those structures are attained, and investigating the effects of directed structural changes on the relevant biomedical systems. The integration of functional genomics with structural questions will allow some of the principal goals of emerging structural genomics efforts to be attained without the need for high-throughput structure determination. The result will be a concentration of expertise in a key area of the molecular biosciences, specifically within the Delaware Biotechnology Institute, which has recently been created at the University. The mission of the center will be implemented via four subprojects spanning the scope of the objectives outlined above: Structure-function relationship of calcium- and integrin-binding protein; Engineering organophosphate hydrolase activity in serine esterases; Functional assays and network modeling to identify the protein sequence- structure-function relation; Synergy of experiment and theory: stability and folding pathways for amyloid and beta-sheet formation. Each subproject is led by one or two assistant professors, with at least one senior collaborator involved to provide both technical collaboration and mentorship. The benefits of the center will also be propagated to other researchers in related areas by virtue of the establishment of core facilities, and the use of cost-sharing funds to support other innovative collaborations in the same vein as the subprojects. In addition, the program will be expanded by addition of two new faculty in proteomics and structural biology, and augmented by an Endowed Chair for whom a search is under way.